Mechanism for the reduction of telomerase expression during muscle cell differentiation.

Telomerase, the reverse transcriptase that maintains telomere DNA, is usually undetectable in adult human tissues, but is positive in embryonic tissues and in cancers. However, in rodents, several organs of normal adult animals express substantial amounts of telomerase activity. To elucidate relevant control mechanisms operating on the tissue-specific expression of telomerase in rodents, we examined the transcriptional regulation of telomerase reverse transcriptase (mTERT) gene in muscle cell differentiation. Reverse transcriptase-polymerase chain reaction analysis showed that the reduction of telomerase activity was caused by the decrease of mTERT mRNA level during myogenesis. Transfections of mTERT promoter showed that the proximal 225-base pair region is the core promoter responsible for basal transcriptional activity and also participates in the reduced transcription after muscle differentiation. Electrophoretic mobility shift assays showed that this region contained the GC-boxes, which bind to Sp1 family proteins, and the E-box, which binds to c-Myc. Furthermore, DNA binding activities of Sp1, Sp3, and c-Myc were down-regulated during myogenesis. These data suggest that Sp1, Sp3, and c-Myc have critical roles of TERT transactivation in mouse, and the lack of these transcription factors cause down-regulation of mTERT gene expression in muscle cells differentiation.